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Effects of Periconception Iron Supplementation on the Penetrance of Neural Tube Defects Open Access

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Neural tube defects (NTDs) are common congenital abnormalities that arise when the neural tube does not close properly during embryogenesis, leading to severe lifelong complications and perinatal death. Current clinical measures used to reduce the risk of a NTD- affected pregnancy is an increase in periconception maternal nutrition, most notably the addition of 4mg of folic acid daily before and throughout pregnancy. The mutant mouse line, Fpn1ffe, contains a hypomorphic mutation, which causes reduced iron transport from mother to embryo during pregnancy and NTD phenotypes in the developing embryos. In this study, we investigated the ability of periconception iron supplementation to alter the penetrance of NTDs in the Fpn1ffe mutant mouse line. We found that by including 0.5% additional carbonyl iron to the maternal diet three weeks before pregnancy was established, NTD penetrance was reduced by 50% compared to both control and folic acid (10 ppm) supplemented diets. Maternal nutrient analysis determined that supplementing iron and folic acid (10 ppm) concurrently, iron negatively impacts folate absorption, whereas folate levels do not alter iron status in the pregnant dams. Additionally, iron supplementation was able to rescue forebrain truncations observed in Fpn1ffe/ffe mutants. This study indicates a requirement for iron during embryogenesis for proper neural tube closure and supports the concept that iron supplementation might prevent NTDs in human pregnancy.

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